Bhadra Pranab K, Magwaza Rachael N, Nirmalan Niroshini, Freeman Sally, Barber Jill, Arsic Biljana
Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
School of Science, Engineering & Environment, University of Salford, Manchester M5 4WT, UK.
Materials (Basel). 2021 Nov 18;14(22):6980. doi: 10.3390/ma14226980.
Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their molecular docking into segments of the exit tunnel of the apicoplast ribosome from . This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of with low micro-molar IC values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC of 68.6 µM, -erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of . Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with constructed segment from the exit tunnel from the apicoplast of . is the reason for their weak in vitro anti-malarial activities.
红霉素A是一种公认的抗革兰氏阳性菌的抗菌剂，但它对酸不稳定。这导致了对红霉素B及其衍生物的评估，因为它们具有更好的酸稳定性。通过将这些化合物分子对接至恶性疟原虫顶质体核糖体出口通道的片段，对它们的抗疟活性进行了研究。据信这是红霉素A衍生物阿奇霉素的作用靶点，阿奇霉素具有轻微的抗疟活性。在多药（氯喹、乙胺嘧啶和磺胺多辛）耐药的恶性疟原虫K1株上，对红霉素B衍生物进行了非同步培养的无性生长抑制评估。在72小时周期后，红霉素B衍生物被鉴定为恶性疟原虫无性生长的体外活性抑制剂，其微摩尔IC值较低。5-去氧氨基糖基红霉内酯B琥珀酸乙酯在多药耐药的恶性疟原虫K1株上显示出低至68.6 μM的IC值，β-红霉素B为86.8 μM，红霉素B 9-肟为146.0 μM。基于分子对接，似乎红霉素B的少数研究衍生物与恶性疟原虫顶质体出口通道构建片段存在少量有利相互作用或不利相互作用，这是它们体外抗疟活性较弱的原因。
